tbuckley/cabot-search huggingface dataset:
PB1708: CHARACTERIZATION OF GLOBAL CYTOGENOMICS FEATURES IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA BY OPTICAL GENOME MAPPING
Authors: Elena Garcia Sanchez, Jorge García, Ana Gomez, Reyes Giménez, David Ruano, Maitane Andion, Lorea Abad, Ana Castillo, Luis Madero, Manuel Ramirez Orellana
Journal: HemaSphere (2023)

Topic: 1. Acute lymphoblastic leukemia - Biology & Translational Research Background: Childhood acute lymphoblastic leukemia (cALL) is the most common childhood malignancy comprising multiple genetic alterations, i.e., structural and sequence mutations. In the past few years, great advances in understanding the biology of cALL by molecular and cytogenetic techniques such as next generation sequencing, karyotyping and FISH have been achieved. Optical Genome Mapping (OGM) has recently arises as a new technology capable of describing whole genome structural and copy number variations with a higher resolution than conventional cytogenetic techniques. Aims: To identify global cytogenomic alterations in diagnostic samples of cALL by OGM. Methods: Cellular samples from diagnostic bone marrow aspirates of 97 patients with cALL were processed for OGM. In brief, the ultra-high molecular weight gDNA from cALL samples was extracted, labelled and loaded into chips to run in the Saphyr platform (Bionano Genomics). Collected data was analyzed by Bionano Access 1.6 software. A binary matrix (presence/absence of each genomic alterations) was created with the chromosomal variants data, then clustering tests were performed to assess for clinical correspondence. In addition, all chromosomal variations were annotated to identify the genes involved. Furthermore, enrichment studies were performed to identify altered cellular pathways and a linkage test was carried out by the STRING interaction database. Results: We obtained a full concordance with previously diagnostic results obtained by conventional cytogenetic techniques and also found novel variants that may help in classification and could indicate common processes required for the development of ALL. CNVs losses and deletions represented almost 50% of all chromosomal alterations found. The number of alterations was diverse among patients ranging from 3 to 300 per sample. Clusters provided by K-Means algorithm based in chromosomal alterations were significantly correlated with lineage. The enrichment analysis identified recurrent involvement of known important pathways in leukemia, such as JAK-STAT. Moreover, an abundant number of immune pathways were altered, particularly those in lost regions, suggesting that the loss of immune functions probably is key for leukemia development. Network protein interaction using STRING database corroborated the involvement of the above mentioned pathways. Summary/Conclusion: The analysis of cytogenomic variations by OGM emerges as a powerful tool to improve the knowledge of the events that underlie cALL biology. Keywords: Cytogenetics, Chromosomal abnormality, Acute lymphoblastic leukemia, Childhood
PB2600: BLOOD TRANSFUSION IN CARDIAC PATIENTS IN CONSTANTA EMERGENCY COUNTY CLINICAL HOSPITAL
Authors: Iulia Andreea, Ali Sevigean
Journal: HemaSphere (2023)

Topic: 31. Transfusion medicine Background: Anemia is common in cardiac patients and affects prognosis. “Even moderate levels of anaemia are associated with increased cardiovascular mortality compared with normal hemoglobin values in the context of acute coronary syndromes.” [1]. Anemia is a comorbidity potentially treatable, with significant prognostic implications. A restrictive transfusion is triggered by hemoglobin is ≤8g/dl (severe anemia) and a liberal transfusion is considered when hemoglobin ≤10 g/dL. Aims: Were analysed the results of blood transfusions in patients from the Cardiology ward of the County Emergency Clinical Hospital Constanța, during one year 2021 Methods: Analysis was realized on 270 patients from cardiology ward, who received red packed cell transfusions, following the efficiency of transfusion by increase in hemoglobin level and improvement of clinical outcome. Results: The majority of patients received a single blood unit 63 % and 37% were polytransfused. The mean hemoglobin (Hb) before transfusions was 7.83g/ dl (6.10g/dl-10.80g/dl) and reached 9.03g/dl (7.10g/dl-11.80g/dl). In patients who received a single blood unit, was observed an increase of 1-2.2 g/dl and in polytransfused the increse of hemoglobin was 2-3,5 g/dl Summary/Conclusion: Rapid correction of anaemia by transfusion was a key factor in the increase of hemoglobin, the goal Hgb 10-11 g/dl correcting the Oxygen supply, vital for the proper functioning of organism processes and saving the pacient,s live. Keywords: Blood transfusion
PB1745: SURVIVAL AND PROGNOSTIC FACTORS OF PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA IN OMAN.
Authors: Moza Almamari, Laila Alkhanbashi, Murtadha Alkhabouri, Abdul Hakim Al Rawas, Suha Albusaidi, Ruqia Albulushi, Amr Abdalla, Yasser Wali
Journal: HemaSphere (2023)

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: Acute lymphoblastic leukemia (ALL) accounts for 25% to 30% of overall childhood cancer and contributes to 43% of deaths among pediatric patients with leukemia with marked improvement in survival over the last decades. Aims: This study aims to assess the outcome of pediatric ALL in Sultan Qaboos University Hospital (SQUH) in Oman. Methods: This is a retrospective longitudinal cohort study which included all pediatric ALL patients at SQUH from 2006 to 2020. Data were collected from electronic patient records. It included patients’ demographic data, clinical symptoms, biochemical markers, bone marrow morphology, cytogenetics and remission check by flow cytometry. Treatment dates and the protocol used, as well the use of herbal medicine. The patient outcomes including continuous remission, relapse or death were recorded. Results: Out of 119 patients with ALL, 90% were below the age of 10 years and 57% were males. Pallor and fever were the most common presenting symptom. Tumor lysis syndrome was diagnosed in 35% of the patients and CNS involvement in fifteen patients. 94% had WBC at presentation of less than 50 × 109/L. The molecular cytogenetics were variable. Measurable residual disease (MRD) was negative in 89 patients. Relapse rate was 8.4% while death rate was 9%. The overall survival over the study period was 92.5% while the event free survival was 91.6% Fig. 1. Summary/Conclusion: In conclusion, our study reported a comparable overall and event free survival to the international standards. A continuation of the registry of the pediatric leukemia patients in a prospective study is highly recommended.Keywords: Acute lymphoblastic leukemia, Acute leukemia
PB1973: MOLECULAR PATTERNS OF RESPONSE AFTER FRONTLINE TREATMENT IN CHRONIC MYELOID LEUKAEMIA (CML).
Authors: Harberth Fernandez-Leyva
Journal: HemaSphere (2023)

Topic: 8. Chronic myeloid leukemia - Clinical Background: An early molecular response (EMR) has a strong predictive value in chronic phase - chronic myeloid leukaemia (CP- CML) and early response landmarks may identify the high-risk patients, likely to benefit from an early therapy switch. Halving time (velocity of early BCR-ABL1 transcript elimination) has been shown to represent an additional prognostic index. Aims: In this study, we evaluated the most relevant cut offs for early molecular response markers (BCR-ABL1 values at 3 months, log reduction and halving time between diagnosis and 3 months) in 51 first-line treated patients with CP- CML. Methods: Our objective was the evaluation of the prognostic significance of the 3-month point in our population. We retrospectively collected BCR-ABL1 transcript data at different time points, events, and survival data of patients with CML treated at the 2 centers of 51 patients diagnosed from January 2020 to November 2022 and treated with front-line tyrosine kinase inhibitors (imatinib, nilotinib and dasatinib), we selected those who had undergone a molecular evaluation at 3 months. Results: We examined relationships between molecular response (MR). MR values were represented by a log-reduction scale (MRLR; a continuous variable). A repeated-measures longitudinal model was used to estimate the relationships MRLR outcome. Effect sizes were calculated to determine strength of effects and allow comparisons across domains via multivariate regression analysis. All outcomes were significantly superior for patients with 3-month BCR-ABL1 ≤ 10%, so did the patients with BCR-ABL1 > 0.6 log reduction. BCR-ABL1 halving time by ≤ 25 days was identified for patients with the most favorable outcome. The prognosis was significantly poorest for patients for both halving the time > 45 days and BCR-ABL1 > 10%. Importantly, the event-free survival (EFS) by the median follow-up time was the primary endpoint. Overall, 71% had a transcript ≤ 10% at 3 months. Of those in the > 10% group, 69 % had experienced an event compared with 12% in the ≤ 10% group by the median follow-up point (P <.001) Summary/Conclusion: We highlighted BCR-ABL1 log reduction outcome and have a clinical relevance to patients with CP- CML receiving tyrosine kinase-based combination therapies. BCR-ABL1 log reduction calculated at 3 months of 0.6 was identifying variable that potentially predicted for OS.Keywords: Chronic myeloid leukemia
PB2561: DEVELOPMENT OF COLD AGGLUTININ AUTOIMMUNE HEMOLYTIC ANEMIA DURING TREATMENT FOR PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA: A CASE REPORT.
Authors: Nabila Haddad, Samia Abdi
Journal: HemaSphere (2023)

Topic: 28. Enzymopathies, membranopathies and other anemias Background: Autoimmune hemolytic anemia (AIHA) is a well-characterized complication of many lymphoid malignancies. Those most often associated with AIHA include chronic lymphocytic leukemia and B-cell lymphomas, and are clonal populations of mature B cells. AIHA in acute lymphoblastic leukemia (ALL) is a rare event. It has been reported in a very few patients after hematopoietic stem cell transplant (HSCT), and only in one case during chemotherapy while in remission. Aims: We describe a child with B-cell precursor ALL who developed cold agglutinin AIHA during maintenance treatment. Methods: The CBC of an 15-year old girl, with B-ALL during maintenance treatment, revealed the following results: Hb:11,2 g/dl; red blood cell (RBC) count:0,26×106/µl, Hematocrit: 2,7%, MCV: 103,8 fl, mean corpuscular hemoglobin (MCH): 430,8 pg, and mean corpuscular hemoglobin concentration (MCHC): 414,8%. Results: RBC clumps that resolved after sample incubation at 37°C suggested the diagnosis of cold agglutinin disease. The direct antiglobulin test (DAT) was positive and the strength of the DAT reactivity increased with cold temperature. Tests for cold agglutinins (4°C) were positive, which confirmed its specificity as auto-anti-I (IgM) with a titer of (1:64). A very low level of haptoglobin (<0.02 g/l) confirmed the haemolysis in our patient. The physical examination of the patient revealed flu syndrome, with acrocyanosis in colder peripheral tissues. A respiratory infection for mycoplasma pneumonia was suggested. Thus, treatment with Josacine was initiated. All hematologic parameters normalized completely, as assessed by CBC at 2 weeks after diagnosis. Summary/Conclusion: Due to both its rarity and limited findings on physical examination, diagnosing AIHA-CA can be difficult. Because many patients with cold agglutinins may never develop any symptoms. Most cases of AIHAI-CA in malignant mature B-cell lymphoid proliferations occur during the active phase of the disease. However, the patient described here developed an AIHA-CA while she was in remission at the end of treatment. It is unknown whether the development of CA-AIHA in the patient described here was due to the underlying malignancy or the respiratory infection. Keywords: Autoimmune hemolytic anemia (AIHA)
P1647: CHRONIC INFLAMMATORY DISEASES INCREASE THE RISK OF POST-THROMBOTIC SYNDROME: A PROSPECTIVE COHORT STUDY
Authors: Aaron F.J. Iding, Thibaut Limpens, Hugo Ten Cate, Arina J. Ten Cate-Hoek
Journal: HemaSphere (2023)

Topic: 34. Thrombosis and vascular biology - Biology & Translational Research Background: Post-thrombotic syndrome (PTS) is a common complication of deep vein thrombosis (DVT). Inflammation is known to play a major pathogenic role in PTS, possibly by promoting residual venous obstruction (RVO). Nevertheless, the potential impact of chronic inflammatory diseases (CIDs) and their anti-inflammatory treatment on the prevalence of PTS has not been studied thus far. Aims: We assessed the risk of PTS in patients with CIDs, stratifying for treatment. Methods: Consecutive patients with proximal DVT were followed prospectively for two years between 2003 and 2020. CIDs included inflammatory bowel disease, rheumatic diseases, and gout. Patients with active malignancy were excluded. RVO was assessed by compressive ultrasound after 3-6 months. PTS was diagnosed using the Villalta score after 6-24 months. Odds ratios (ORadj) were calculated by logistic regression adjusted for relevant patient characteristics. The medical ethics committee approved this study. Results: In total 82 of 801 patients had CIDs (10.2%). Patients with CIDs were older (median 65 vs. 58 years), but similar for other patient characteristics. RVO was more strongly associated with PTS in patients with CIDs (ORadj 4.22 [1.25-14.30]) compared to those without CIDs (ORadj 2.08 [1.37-3.15]). Overall, patients with CIDs had a similar prevalence of RVO (36.8% vs. 41.4%), but more often developed PTS (35.4% vs. 18.9%, p < 0.001) than those without CIDs (ORadj 2.37 [1.39-4.06]). In patients with CIDs that received anti-inflammatory treatment (n=46, 56%), the prevalence of RVO was much lower than in those with untreated CIDs (26.1% vs. 53.3%, p=0.027). Accordingly, the risk of PTS was particularly high in patients with untreated CIDs (ORadj 3.56 [1.70-7.43]) compared to those without CIDs (Figure 1). Summary/Conclusion: Patients with CIDs were at an increased risk to develop PTS. Notably, the risk of PTS was lower in patients with treated CIDs, which might be due to a favorable effect of anti-inflammatory treatment on RVO-related venous pathology.Keywords: Inflammation, Deep venous thrombosis, Venous thrombosis, Post-thrombotic syndrome
PB1829: QUERCETIN EXHIBITS ANTI-LEUKEMIA EFFECTS VIA REGULATION OF METABOLIC REPROGRAMMING
Authors: Jing Zhang, Rui-Hua Huan, Yan-Qiu Han#
Journal: HemaSphere (2023)

Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: Quercetin is a flavonoid which exists in multiple foods such as fruit and vegetables. Various studies have indicated that quercetin possesses capacities of anti-oxidant, anti-inflammatory and, especially, anti-cancer effects such as reducing tumor microenvironment components, suppressing carcinoma growth and modulating metabolic reprogramming in tumor cells. Previous experiments demonstrated that quercetin could inhibit the cell viability of primary and P388 AML cells in vitro, but its mechanism remains unclear. Here we speculated that quercetin might mediate its anti-leukemic effects via regulating of metabolic reprogramming. Aims: To analyze the effects of quercetin on the metabolic activity of acute myeloid leukemia cell lines KG-1α and HL-60. Methods: CCK-8 analysis was used to detect the prohibitive effects of quercetin on the proliferation of KG-1α and HL-60 cells, and flow cytometry was used to analyze the apoptosis; Quantitative real time polymerase chain reaction (qRT-PCR) was used to detect the gene expression of AMPK, CPT1A and GLUT1. The contents of ATP and pyruvate were measured to determine the level of cell metabolism. Results: CCK-8 analysis showed the quercetin had a statistically significant inhibitory effect on the proliferation of KG-1α (r24 h= 0.780，r48 h= 0.786，r72 h= 0.796）and HL-60 cells (r48 h= 0.799, r72 h= 0.760）in a dose dependent manner; The flow cytometry results displayed that quercetin promoted the apoptosis of KG-1α（P<0.001） and HL-60 cells（P<0.001）. The PCR results demonstrated that quercetin decreased the expression of AMPK, GLUT1 and CPT1A gene in KG-1α and HL-60 cells（P<0.05）. Moreover, quercetin significantly reduced the level of ATP and pyruvate in KG-1α and HL-60 cells (P < 0.001) Summary/Conclusion: Quercetin inhibited the proliferation of AML cells in a concentration-dependent manner and promoted cell apoptosis rates, which might be regulated by alteration in AMPK, GLUT1 and CPT1A. Quercetin might provide theoretical and experimental basis for treatment in AML. Keywords: Acute myeloid leukemia, AML
PB1837: ANTIBIOTICS; A POSSIBLE ALTERNATE TREATMENT OPTION FOR MYELOID LEUKEMIA
Authors: Syeda Maham, Saba Naseem Awan, Fazal Adnan, Salik Javed Kakar, Afsar Mian, Dilawar Khan
Journal: HemaSphere (2023)

Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: Leukemia is the cancer of white blood cells (WBCs) from myeloid and lymphoid progenitors, which are involved in blood cells production. Based on the progression, myeloid leukemia may be either acute or chronic. This study was focused on Acute promyelocytic leukemia (APL), a sub type of acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Despite the encouraging results of FDA-approved therapies, problem of relapse and adoptive resistance remain the two major clinical challenges in the treatment of leukemia. Gramicidin A, an ionophore and well-known antibiotic, has recently been shown to cause tumor cell death, however its role in leukemia has not been explored. Aims: The aim of this study was to explore the possible anticancer role of Gramicidin A in APL and CML. Methods: We used different in-silico tools, pharmacological and biochemical approaches. Results: we report that Gramicidin A interferes with proliferation potential of APL and CML cell lines (p < 0.05 and (p < 0.0001)). The combined effect of Gramicidin A with imatinib for CML and ATRA for APL showed additive anticancer effect ((p < 0.0001) which was related to AXL-RTK dependent down regulation of β-catenin target genes such as, c-Myc, Eya3, and Axin 2 (p < 0.0001). Further Gramicidin A did not induce any hemolysis of red blood cells which shows its safety with no toxicity. Summary/Conclusion: Our results suggest that gramicidin A strongly interfere with leukemogenic potential of APL and CML without any toxicity and can be a possible alternative candidate for therapeutic interventions in future. Keywords: Leukemia
PB1843: DONOR-DERIVED CLL-1 CHIMERIC ANTIGEN RECEPTOR T-CELLS FOR RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA BRIDGING TO ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION: A CASE REPORT
Authors: Xiaojuan Miao, Yanrong Shuai, Ying Han, Yilan Liu, Hao Yao, Xiao Wang, Guangcui He, Dan Chen, Fangyi Fan, Alex Chang, Yi Su, Hai Yi
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: The prognosis of relapsed/refractory acute myeloid leukemia (R/R AML) is still poor and the treatment remains a challenging issue. Aims: To explore the efficacy and safety of donor-derived CLL-1 chimeric antigen receptor (CAR) T-cell therapy for R/R AML followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) bridging upon remission. Methods: A young male patient (18 years old) was diagnosed with CEBPA double-mutated AML. After initial chemotherapy, he achieved minimal residual disease (MRD)-negative complete remission (CR), that was followed by auto-HSCT. His leukemia disease was relapsed 6 months later. The salvage therapy with azacitidine and venetoclax was not helpful and his disease was deteriorated with 61% blasts in bone marrow (BM) and 63.18% blasts detected by flow cytometry (FCM) with a phenotype positive for CD34, CD117, HLA-DR, CD13, CD33, CD38, CD123 and CLL-1 upon admission. CAR T-cells targeting CLL-1 were manufactured using peripheral blood from a haploidentical donor, he received a total of 0.5*106/kg CAR T-cells with informed consent. The vital signs, complete blood counts, cytokines, serum ferritin, peripheral blood (PB) CAR T-cell counts, BM aspirate and MRD by FCM were monitored. Allo-HSCT from the same donor was started immediately after CR upon BM evaluation. Blood counts, BM aspirate and MRD, graft-versus-host disease (GVHD), and chimerism status were routinely monitored. Results: The patient developed fever at day 8 after CAR T-cells infusion, which peaked at 39.2°C. After supportive care, the temperature returned to normal range at day 10. There were no episodes of hypoxia, hypotension or immune effector cell-associated neurotoxicity syndrome (ICANS). The cytokine release syndrome (CRS) was assessed as grade 1. CAR T-cells expanded in PB at the peak of 9.4% in the whole T cells at day 8. The patient achieved CR with 0.29% MRD in BM by FCM at day 11. He was then bridged to allo-HSCT immediately. He achieved neutrophil engraftment at day 18 and platelet engraftment at day 26 after transplantation. Complete donor chimerism was observed at day 23. MRD negative CR in BM was achieved at day 23. The patient is currently 6 months after transplantation, with sustain MRD negative CR in BM, and no extramedullary disease or GVHD. Summary/Conclusion: Donor-derived CLL-1 CAR T-cell is effective and safe for treating R/R AML. Bridging to allo-HSCT immediately following CR may improve prognosis in these patients' population. (www.chictr.org.cn number, ChiCTR2200058607.) Keywords: AML, CAR-T, Allogeneic stem cell transplant
PB2542: MOLECULAR SPECTRUM OF ALPHA THALASSEMIA MUTATIONS IN THE WESTERN PROVINCE OF SAUDI ARABIA AND RECOMMENDATION FOR PREMARITAL SCREENING
Authors: Samy Attallah, Marwa Alhadad, Wala Alqarni, Doa Filfilan, Ahmed Zaharani, Ahmed Alharby, Ateyah Al Malki, Nawaf Algabry, Ebtihag Jamil, Ahmed Hakami, Samah Mokhles, Jawarrha Almanee, Iman Alhazmi
Journal: HemaSphere (2023)

Topic: 27. Thalassemias Background: Background: α-thalassemia is frequently encountered in Saudi Arabia. There is a large diversity and geographical variability in underlying genotypes in α-thalassemia patients. HGB H disease can be reduced by premarital thalassemia screening. Aims: To characterize the molecular spectrum of α-thalassemia in some Saudi patients suspected of α thalassemia carrier or diagnosed with HGB H disease to determine if there is significance of premarital testing for α thalassemia mutations by PCR in couple with suspected α thalassemia trait. Methods:Patients and methods This study included 39 patients, 34 patients with suspected α thalassemia carrier by having unexplained microcytic hypochromic erythrocytes, with normal iron status and Hb A2 below 3.5%, or being the available parent of a patient with Hb H disease, and 5 patients diagnosed with HGB H disease by HPLC. The 39 patients were screened for 21 α-globin mutations based on polymerase chain reaction (PCR) and reverse-hybridization. Results: Thirteen patients 33.3% are heterozygous for α+ thalassemia having the genotype -α3.7/ αα and 14 patients 35.9% are homozygotes for α0 having the genotype -α3.7/-α3.7 and, one patient with –MED/ αα, one with –SEA/ αα, and one –PA-1/ αα and the 5 patients with HGB H disease 12.8% (0.01% from 30200 HPLC results). one patient has genotype of –SEA/-α3.7 have (3.7 Kb deletion) associated with –SEA. and one with –MED/-α3.7 a Mediterranean thalassemia (–MED) with3.7 kb heterozygous deletion,, and 2 patients with genotype αPA-1 α/ αPA-1α homozygous mutation Poly A (A->G). There was one case with negative molecular screening for α-thalassemia Summary/Conclusion: The -α3.7 was the most common mutation among patients with α-thalassemia forms 69.2 % of all deletions. Del. 3.7 kb is not considered as risky mutation. The premarital genetic diagnosis of α-thalassemia is not recommended in Saudi population as the most common α-thalassemia mutation are -α3.7 deletion which is not risk for hydrops fetalis. Premarital screening should be considered in families with history of HGB H disease or hydropes fetalis and should include both testing for common deletion and mutation DNA sequencing. Keywords: Thalassemia, Molecular